BE779775A - Derives de l'uree, procede pour les preparer et leurs applications - Google Patents

Derives de l'uree, procede pour les preparer et leurs applications

Info

Publication number
BE779775A
BE779775A BE779775A BE779775A BE779775A BE 779775 A BE779775 A BE 779775A BE 779775 A BE779775 A BE 779775A BE 779775 A BE779775 A BE 779775A BE 779775 A BE779775 A BE 779775A
Authority
BE
Belgium
Prior art keywords
emi
group
atom
solution
urea
Prior art date
Application number
BE779775A
Other languages
English (en)
Original Assignee
Smith Kline French Lab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26240626&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BE779775(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB635271A external-priority patent/GB1338169A/en
Application filed by Smith Kline French Lab filed Critical Smith Kline French Lab
Publication of BE779775A publication Critical patent/BE779775A/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/84—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/46—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/36—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Handcart (AREA)

Description


   <EMI ID=1.1> 

  
des procédés pour leur préparation. Les composés suivant l'invention peuvent se présenter sous forme de sels d'addition" mais

  
 <EMI ID=2.1> 

  
Une hypothèse depuis longtemps admise est que beaucoup

  
des substances à activité physiologique se combinent dans le

  
 <EMI ID=3.1> 

  
 <EMI ID=4.1> 

  
mais .comme ses activités sont de plusieurs genres, l'on suppose 

  
qu'il existe plusieurs types de récepteurs d'histamine. Le genre

  
 <EMI ID=5.1> 

  
 <EMI ID=6.1> 

  
le fait qu'ils agissent comme récepteurs d'histamine d'une autre

  
 <EMI ID=7.1> 

  
les composés'faisant l'objet de l'invention peuvent être représentés par la formule. générale ci-après ? étant entendu que

  
 <EMI ID=8.1> 

  
 <EMI ID=9.1> 

  

 <EMI ID=10.1> 


  
 <EMI ID=11.1>   <EMI ID=12.1> 

  
le, bensyle, un atome d'halogène, un groupe amino ou un groupe <EMI ID=13.1> 

  
du groupe A un autre noyau, par exemple un noyau.benzène ou pyrimidine, ou un noyau partiellement insaturé ; 1 et m sont des nom-

  
 <EMI ID=14.1> 

  
un groupe nitro ou cyano. Le groupe A est de -préférence choisi de manière que l'atome d'azote soit adjacent à l'atome de carbone indique et,. mieux encore;qu'il forme avec cet atome de carbone un

  
 <EMI ID=15.1> 

  
 <EMI ID=16.1>   <EMI ID=17.1> 

  
préparés à partir de composés de la formule générale 

  

 <EMI ID=18.1> 


  
 <EMI ID=19.1> 

  
 <EMI ID=20.1> 

  

 <EMI ID=21.1> 


  
 <EMI ID=22.1> 

  
 <EMI ID=23.1> 

  
méthoxy. Le premier stade de cette préparation consiste à faire

  
 <EMI ID=24.1> 

  

 <EMI ID=25.1> 


  
 <EMI ID=26.1> 

  
Lorsque Q est un halogène, cette réaction peut être ef-  fectuée dans des conditions fortement basiques, par exemple en présence d'éthoxyde de sodium ou d'hydroxyde de sodium. Puisque le composé de la formule III est uns amine primaire, il est nécessaire de protéger le groupe amino, par exemple par un groupe  phtal-imido, qui peut ensuite être séparé par hydrolyse acide ou

  
 <EMI ID=27.1> 

  
la réaction s'effectue dans des conditions acides, par exemple en présence d'un acide halohydrique, tel qu'une solution aqueuse à

  
 <EMI ID=28.1> 

  
l'acide acétique glacial. Lorsque Q est un radical méthoxy, la réaction peut également s'effectuer en présence d'une solution  <EMI ID=29.1> 

  
Les produits obtenus par les procédés si-dessus sont des composés de la formule suivante , ou encore les sels d'addition .

  
 <EMI ID=30.1> 

  

 <EMI ID=31.1> 


  
 <EMI ID=32.1> 

  
3.' on fait réagir dans un solvant approprié, tel que le chloroforme, avec, un isothiocyanate d'acyle. Une hydrolysa alcaline du 

  
 <EMI ID=33.1> 

  
 <EMI ID=34.1> 

  
me d'hydrogène et Y et E -sont des atomes de soufre: peuvent également être préparésdirectement par la réaction à température

  
 <EMI ID=35.1> 

  
nium ou d'un métal tel que le sodium ou le potassium. 

  
 <EMI ID=36.1>   <EMI ID=37.1> 

  

 <EMI ID=38.1> 


  
 <EMI ID=39.1> 

  
 <EMI ID=40.1> 

  
 <EMI ID=41.1> 

  

 <EMI ID=42.1> 


  
 <EMI ID=43.1>   <EMI ID=44.1> 

  

 <EMI ID=45.1> 


  
Les composés de la formule VII peuvent être transformés en des 

  
 <EMI ID=46.1> 

  
décrites ci-dessus pour la transformation des composés de la for-

  
 <EMI ID=47.1> 

  
 <EMI ID=48.1> 

  
Les composés de la formule 1, pour lesquels Y est un

  
 <EMI ID=49.1> 

  
nière semblable au départ d'un composé de la formule : 

  

 <EMI ID=50.1> 


  
 <EMI ID=51.1> 

  

 <EMI ID=52.1> 


  
 <EMI ID=53.1>  
 <EMI ID=54.1> 
 <EMI ID=55.1>  tant qu'inhibiteurs de certaines actions de l'histamine,qui ne

  
 <EMI ID=56.1> 

  
ne"- C'est ainsi que l'on a constaté qu'ils inhibent sélectivement la sécrétion de l'acide ; gastrique, -stimulée par l'histamine,

  
 <EMI ID=57.1> 

  
ventricule droit isolé de cobaye et l'utérus isolé du rat. les

  
 <EMI ID=58.1> 

  
un aliment..' .

  
Le taux d'activité de. compositions' contenant les dérivés <EMI ID=59.1> 

  
tration sous forme d'une composition pharmaceutique, qui contient:
comme ingrédient actif essentiel, ou comme ]:'un- de ses ingrédients - 

  
 <EMI ID=60.1> 

  
 <EMI ID=61.1> 

  
de comprimés , en capsules, en solution injectable ou comme crème   <EMI ID=62.1> 

  
pour des applications locales. "$la

  
1" invention est décrite si-après plus en détail à l'aide

  
 <EMI ID=63.1>  on refroidit la solution jaune obtenue sur un bain de sel et de glacé. puis on ajoute goutte à goutte, en l'espace de 10 minutes, 

  
 <EMI ID=64.1> 

  
té par addition d'eau et séparé par filtration" Le filtrat est .concentré et alcalinisé avec une solution aqueuse, de bicarbonate <EMI ID=65.1>   <EMI ID=66.1>  lendemain à la température ordinaire), puis filtré et le filtrat acidifié avec de l'acide chlorhydrique concentré. La 'solution est ensuite évaporée à siccité et au résidu dissous dans l'étha-

  
 <EMI ID=67.1> 

  
 <EMI ID=68.1> 

  
traite par l'alcool isopropyliquep pour la séparer des produits  inorganiques,et les extraits sont concentrés jusque environ 70

  
 <EMI ID=69.1> 

  
froidissement évaporé à siccité. S'imite résiduelle est dissoute

  
 <EMI ID=70.1>   <EMI ID=71.1>  
 <EMI ID=72.1> 
 <EMI ID=73.1> 

  
 <EMI ID=74.1> 

  
 <EMI ID=75.1> 

  
méthyle dans des conditions semblables à celles décrites dans .

  
 <EMI ID=76.1> 

  
 <EMI ID=77.1> 

  
 <EMI ID=78.1>  <EMI ID=79.1> 

  
 <EMI ID=80.1>   <EMI ID=81.1> 

  
vie d'une agitation de 3 heures à la température ambiante'- on a-

  
 <EMI ID=82.1> 

  
 <EMI ID=83.1> 

  
hydrogéné à la température ordinaire et à la pression atmosphérique jusqu'à absorption de la quantité théorique d'hydrogène,, Après filtration du mélange, le filtrat est concentré et par ad-

  
 <EMI ID=84.1>   <EMI ID=85.1> 

  
g) avec le nitrite de sodium, suivie de la réduction du 2-oximino-3-oxo-4-phényl-butyrate d'éthyle brut (10,8 g), comme décrit

  
 <EMI ID=86.1> 

  
En suivant le mode opératoire du chapitre (b) précé-

  
 <EMI ID=87.1> 

  
 <EMI ID=88.1>   <EMI ID=89.1> 

  
obtient un solide, qui est recueilli après concentration par-  tielle et donne par recristallisation, dans l'acétate d'éthyle la

  
 <EMI ID=90.1>  
 <EMI ID=91.1> 
 pour laquelle le tableau II indique les diverses significations

  
 <EMI ID=92.1> 

  

 <EMI ID=93.1> 


  
 <EMI ID=94.1> 

  
sous atmosphère d'azote. Après addition complète, la solution

  
 <EMI ID=95.1> 

  
 <EMI ID=96.1> 

  
tente de quelques gouttes de la solution d'hydroxyde de potas-

  
 <EMI ID=97.1>   <EMI ID=98.1>  <EMI ID=99.1> 

  
 <EMI ID=100.1> 

  
 <EMI ID=101.1> 

  
On maintient la solution à cette température pendant 1 heure, _ 

  
 <EMI ID=102.1>   <EMI ID=103.1> 

  
mélange alcool isopropylique-acétate d'éthyle-éther). Par recris-

  
 <EMI ID=104.1>   <EMI ID=105.1> 

  
 <EMI ID=106.1> 

  
 <EMI ID=107.1> 

  
 <EMI ID=108.1>  <EMI ID=109.1> 

  
tenir après évaporation du mélange réactionnel un solide jaune

  
 <EMI ID=110.1> 

  
 <EMI ID=111.1> 

  
 <EMI ID=112.1>  

  

 <EMI ID=113.1> 


  
 <EMI ID=114.1> 

  
! noyau, le solvant employé pour la recristallisation du produit,

  
 <EMI ID=115.1> 

  
 <EMI ID=116.1> 

  
 <EMI ID=117.1> 

  
(i) En agitant, on ajoute de l'acide chlorhydrique (90 ml)

  
 <EMI ID=118.1> 

  
séparation des produits inorganiques par filtration, on ajoute

  
 <EMI ID=119.1> 

  
heures, à reflux. Par concentration et refroidissement, on obtient un solide blanc,.qui par recristallisation dans l'éthanol

  
 <EMI ID=120.1> 

  
propyle (13,4 g), on chauffe la solution obtenue à reflux pendant 2,5 heures, puis on concentre sous pression réduite. -le

  
 <EMI ID=121.1> 

  
(iii) A une solution de 2-(3-phtalimido-propylthio)-oxazole
(10 g) dans l'éthanol (173 ml), maintenue en agitation* on ajou-

  
 <EMI ID=122.1> 

  
chauffe la solution à reflux pendant 25 minutes. Après refroidissement, on sépare l'hydraside phtalique par filtration, on

  
 <EMI ID=123.1> 

  
 <EMI ID=124.1> 

  
pylthio)-oxazole brut, qui est lavé deux fois à l'éther et disvous dans l'éthanol (60 ml). Après addition d'isothiocyanate de méthyle (2,54 g), la solution est chauffée à reflux pendant 30

  
 <EMI ID=125.1> 

  
 <EMI ID=126.1>   <EMI ID=127.1> 

  
(ii) Le traitement du dérivé de phtalimide ci-dessus,' (3 "0

  
 <EMI ID=128.1> 

  
 <EMI ID=129.1> 

  
 <EMI ID=130.1> 

  
 <EMI ID=131.1> 

  
 <EMI ID=132.1> 

  
 <EMI ID=133.1> 

  
produit est ensuite alcalinisé.par du carbonate de potassium

  
 <EMI ID=134.1> 

  
l'alcool isopropylique (3 x 50 ml). La concentration des ex-:- 

  
 <EMI ID=135.1>   <EMI ID=136.1> 

  
purifié par chromatographie sur une colonne de gel de Milice,

  
 <EMI ID=137.1> 

  
d'alumine, avec le chloroforme comme éluant. Après recristallisa-

  
 <EMI ID=138.1>   <EMI ID=139.1> 

  
dans de l'eau (50 ml) est chauffée à reflux pendant 3 heures.',  Âpres concentration à faible volume et acidification par de l'a-

  
 <EMI ID=140.1> 

  
dans le méthanol (35 ml) est chauffée pendant 2,5 heures entre
50 et 60[deg.]0 et puis laissée au repos.à la température ordinaire pendant 48 heures. Le produit cristallisé est séparé par filtra-

  
 <EMI ID=141.1> 

  
 <EMI ID=142.1>   <EMI ID=143.1>  
 <EMI ID=144.1> 
 <EMI ID=145.1> 
 
 <EMI ID=146.1> 
 <EMI ID=147.1> 
 
 <EMI ID=148.1> 
 <EMI ID=149.1> 
 
 <EMI ID=150.1> 
 <EMI ID=151.1> 
 
 <EMI ID=152.1> 
 <EMI ID=153.1> 
 
 <EMI ID=154.1> 
 <EMI ID=155.1> 
 
 <EMI ID=156.1> 
 <EMI ID=157.1> 
 
 <EMI ID=158.1> 
 <EMI ID=159.1> 
 
 <EMI ID=160.1> 
 <EMI ID=161.1> 
 
 <EMI ID=162.1> 
 <EMI ID=163.1> 
 
 <EMI ID=164.1> 
 <EMI ID=165.1> 
 
 <EMI ID=166.1> 
 <EMI ID=167.1> 
 
 <EMI ID=168.1> 
 <EMI ID=169.1> 
 
 <EMI ID=170.1> 
 <EMI ID=171.1> 
 
 <EMI ID=172.1> 
 <EMI ID=173.1> 
 
 <EMI ID=174.1> 
 <EMI ID=175.1> 
  <EMI ID=176.1> 

  

 <EMI ID=177.1> 


  
dans laquelle le symbole A désigne un groupe qui forme avec l'atome de carbone indiqué un noyau hétérocyclique non saturée qui contient au moins un atome d'azote et peut comporter d'autres  hétéro-atomes, comme le soufre et l'oxygène j les symboles X et. qui peuvent être identiques ou différents, désignent chacun un atome d'hydrogène, un radical alcoyle inférieur, trifluoro-

  
 <EMI ID=178.1> 

  
groupe

  

 <EMI ID=179.1> 


  
 <EMI ID=180.1> 

  
 <EMI ID=181.1> 

  
 <EMI ID=182.1> 

  
symbole Y désigne un atome d'oxygène ou de soufre ou un groupe

  
 <EMI ID=183.1> 

  
groupe A ferme un noyau autre qu'un noyau pyridine, un groupe

  
 <EMI ID=184.1> 

  
 <EMI ID=185.1> 

  
 <EMI ID=186.1> 

  
d'hydrogène, ; un groupe nitro ou cyano.

Claims (1)

  1. 2;- Composé suivant la revendication 1, caractérisé en ce que le noyau hétérocyclique non saturé de base contient <EMI ID=187.1>
    en ce que X et X , qui peuvent être identiques ou différents, . désignent chacun un atome d'hydrogène, un radical alcoyle infé-
    <EMI ID=188.1>
    <EMI ID=189.1>
    <EMI ID=190.1> <EMI ID=191.1>
    2 à 4 et E désigne un atome d'oxygène ou de soufre.
    <EMI ID=192.1>
    <EMI ID=193.1>
    désignent chacun un atome.d'hydrogène}, un radical alooyle infé.rieur ou, benzyle 'ou un atone d'halogène et 1 est un.nombre entier
    <EMI ID=194.1>
    <EMI ID=195.1>
    gène, un radical méthyle, un atome de brome, un radical amino ou
    <EMI ID=196.1>
    <EMI ID=197.1>
    <EMI ID=198.1>
    en ce qu&#65533; le noyau hétérocyclique non saturé est un noyau imida-
    <EMI ID=199.1>
    <EMI ID=200.1>
    <EMI ID=201.1>
    <EMI ID=202.1>
    21.-Compositions pharmaceutiques, contenant comme ingrédient. actif, ou comme l'un des ingrédients actifs, une quantité efficace d'un composé suivant l'une ou-l'autre des reTendi-
    <EMI ID=203.1>
    <EMI ID=204.1>
    <EMI ID=205.1>
    groupe <EMI ID=206.1> <EMI ID=207.1>
    <EMI ID=208.1>
    <EMI ID=209.1>
    <EMI ID=210.1>
    <EMI ID=211.1>
    <EMI ID=212.1>
    <EMI ID=213.1>
BE779775A 1971-03-09 1972-02-24 Derives de l'uree, procede pour les preparer et leurs applications BE779775A (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB635271A GB1338169A (en) 1971-03-09 1971-03-09 Ureas thioureas and guanidines
GB3433471 1971-07-22

Publications (1)

Publication Number Publication Date
BE779775A true BE779775A (fr) 1972-08-24

Family

ID=26240626

Family Applications (1)

Application Number Title Priority Date Filing Date
BE779775A BE779775A (fr) 1971-03-09 1972-02-24 Derives de l'uree, procede pour les preparer et leurs applications

Country Status (21)

Country Link
JP (5) JPS5324422B1 (fr)
AR (2) AR197080A1 (fr)
BE (1) BE779775A (fr)
CY (1) CY856A (fr)
DK (1) DK139870B (fr)
EG (1) EG10876A (fr)
ES (1) ES400587A1 (fr)
FI (1) FI60393C (fr)
HK (1) HK55176A (fr)
HU (1) HU164509B (fr)
IE (1) IE36050B1 (fr)
IL (1) IL38821A (fr)
IT (1) IT1041101B (fr)
KE (1) KE2625A (fr)
MY (1) MY7600228A (fr)
NO (1) NO133196C (fr)
PH (2) PH12207A (fr)
SE (3) SE402288B (fr)
SG (1) SG28576G (fr)
SU (1) SU460628A3 (fr)
ZM (1) ZM3672A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2344833A1 (de) * 1972-09-05 1974-03-14 Smith Kline French Lab Guanidine, ihre salze, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE2344779A1 (de) * 1972-09-05 1974-03-14 Smith Kline French Lab Cyanguanidine, ihre salze, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
US4000296A (en) * 1972-09-05 1976-12-28 Smith Kline & French Laboratories Limited Imidazole alkylguanidine compounds
US4083988A (en) * 1972-09-05 1978-04-11 Smith Kline & French Laboratories Limited Pharmacologically active compounds
US4129657A (en) 1975-03-21 1978-12-12 Smith, Kline & French Laboratories Limited Imidazole guanidines and use as inhibitors of histamine activity

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL56265A (en) * 1977-12-28 1982-08-31 Om Lab Sa Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor
JPH07107054B2 (ja) * 1987-05-20 1995-11-15 株式会社日本触媒 ４−メチル−５−〔（２−アミノエチル）チオメチル〕イミダゾ−ル二塩酸塩の製法
JP2933739B2 (ja) * 1990-04-09 1999-08-16 明治製菓株式会社 チアゾールまたはイミダゾール誘導体および抗潰瘍剤

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2344833A1 (de) * 1972-09-05 1974-03-14 Smith Kline French Lab Guanidine, ihre salze, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE2344779A1 (de) * 1972-09-05 1974-03-14 Smith Kline French Lab Cyanguanidine, ihre salze, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
US4000296A (en) * 1972-09-05 1976-12-28 Smith Kline & French Laboratories Limited Imidazole alkylguanidine compounds
US4083988A (en) * 1972-09-05 1978-04-11 Smith Kline & French Laboratories Limited Pharmacologically active compounds
US4129657A (en) 1975-03-21 1978-12-12 Smith, Kline & French Laboratories Limited Imidazole guanidines and use as inhibitors of histamine activity

Also Published As

Publication number Publication date
IE36050L (en) 1972-09-09
EG10876A (en) 1976-07-31
CY856A (en) 1976-09-10
ES400587A1 (es) 1975-07-16
IL38821A (en) 1975-05-22
AR197093A1 (es) 1974-03-15
JPS53119867A (en) 1978-10-19
JPS5742068B2 (fr) 1982-09-07
SE410103B (sv) 1979-09-24
JPS5324422B1 (fr) 1978-07-20
SE402288B (sv) 1978-06-26
NO133196B (fr) 1975-12-15
SG28576G (en) 1987-04-03
DK139870C (fr) 1979-10-08
PH12247A (en) 1978-12-12
IE36050B1 (en) 1976-08-04
HU164509B (fr) 1974-02-28
HK55176A (en) 1976-09-17
JPS5811948B2 (ja) 1983-03-05
FI60393C (fi) 1982-01-11
AR197080A1 (es) 1974-03-15
SE7412680L (fr) 1974-10-09
JPS5732063B2 (fr) 1982-07-08
IT1041101B (it) 1980-01-10
FI60393B (fi) 1981-09-30
NO133196C (fr) 1976-03-24
SE430689B (sv) 1983-12-05
MY7600228A (en) 1976-12-31
SU460628A3 (ru) 1975-02-15
PH12207A (en) 1978-11-29
JPS53119868A (en) 1978-10-19
DK139870B (da) 1979-05-07
KE2625A (en) 1976-05-28
SE7610842L (sv) 1976-09-30
IL38821A0 (en) 1972-10-29
JPS53119869A (en) 1978-10-19
JPS5459275A (en) 1979-05-12
ZM3672A1 (en) 1972-10-23

Similar Documents

Publication Publication Date Title
EP0591057B1 (fr) Arylalkyl(thio)amides ayant une affinité sélective pour les récepteurs de la mélatonine et leur procédé de préparation
EP0399856B1 (fr) Pteridin-4 (3H)-ones, procédés de préparation et médicaments les contenant
LU79761A1 (fr) Procede de preparation de nouveaux composes de phtalazine et de composition pharmaceutique les contenant
CH619463A5 (fr)
EP0459887A1 (fr) Dérivés N-pyrazolyl-ortho-dialkyl-benzamide doués d&#39;activité anticonvulsivante, procédé de préparation et composition pharmaceutique
EP0624575A1 (fr) Indoles substitués et les compositions pharmaceutiques qui les contiennent
EP0073161A1 (fr) Nouveaux dérivés de la pyrazine actifs sur le système nerveux central
EP0117771B1 (fr) Imino-2 pyrrolidines, leur procédé de préparation et leurs applications en thérapeutique
BE779775A (fr) Derives de l&#39;uree, procede pour les preparer et leurs applications
WO1993020046A1 (fr) Derives d&#39;indane-1,3-dione et d&#39;indane-1,2,3-trione, leurs procedes de preparation et leur application en therapeutique
EP0021940A1 (fr) Nouveaux dérivés aminés du benzothiazole, leur procédé de préparation et leur application en thérapeutique
FR2534582A1 (fr) Nouveaux derives de benzofuranne et de benzothiophene, utiles comme agents anti-hyperuricemie et anti-hypertension, et leur procede de fabrication
BE884387A (fr) Composition a base d&#39;acides aryloxyalkylaminobenzoiques, leurs sels et leurs esters
CH407088A (fr) Procédé de préparation de dérivés des acides 4-halo-3-sulfamoyl-benzoïques
FR2551063A1 (fr) Nouveaux dimethyl-2,5 pyrroles, leur procede de preparation et leur application en therapeutique
EP0000452B1 (fr) Dérivés d&#39;oxadiazole-1,2,4, leur préparation et leur application en thérapeutique.
CH650254A5 (fr) Quinolones, leurs procedes de preparation et compositions therapeutiques les contenant.
EP0002401B1 (fr) Dérivés de naphtalène, leur préparation et leur application en thérapeutique
CA1211105A (fr) Procede pour la preparation de derives de p-acylaminophenol et derives obtenus par ce procede
EP0294258A1 (fr) Dérivés d&#39;hydrazine, procédé d&#39;obtention et compositions pharmaceutiques les contenant
EP0275221B1 (fr) Nouveaux dérivés du N-(1H-indol 4-yl) benzamide ainsi que leurs sels, leur application à titre de médicaments et les compositions les renfermant
WO2000063170A1 (fr) Derives de cyclobutene-3,4-dione en tant qu&#39;inhibiteurs de la phosphodiesterase 5
CH392483A (fr) Procédé de préparation de nouveaux esters d&#39;acides 4-halo-3-sulfamoyl-benzoïques
BE858864A (fr) Nouveaux esters d&#39;acides phenyl- et pyridine-3-carboxylique et procede permettant leur preparation
CH639374A5 (fr) N-(4-pyrazolidinyl)-benzamides, presentant notamment des proprietes antiemetiques et de vidage gastrique.

Legal Events

Date Code Title Description
RE20 Patent expired

Owner name: SMITH KLINE & FRENCH LABORATORIES LTD

Effective date: 19920224